miR-139-5p targeting DNMT1 inhibits the growth and metastasis of glioblastoma / 西安交通大学学报(医学版)

【Objective】 To investigate the expression and biological role of miR-139-5p in glioblastoma and the regulatory effect of miR-139-5p on DNA methyltransferase 1 (DNMT1). 【Methods】 qRT-PCR was used to detect the expression of miR-139-5p in glioblastoma tumor tissue, paired paracancerous tissue, human normal glioma cell line HEB, and human glioma cell line U251. The expression of miR-139-5p in U251 cells was up-regulated by transfection of miR-139-5p mimetics, and the expression of DNMT1 was down-regulated by transfection of DNMT1-targeted siRNA (DNMT1-siRNA). The expression of DNMT1 and neurofibromatosis type 2 (NF2) in tissues and cells was detected by qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence. The cell counting kit-8 (CCK-8), flow cytometry and Matrigel Transwell were used to evaluate the proliferation, apoptosis and invasion ability of U251 cells. 【Results】 Compared with paracancerous tissues or HEB cells, miR-139-5p expression in glioblastoma tissues and U251 cells was suppressed (P<0.05). Compared with control cells, transfection of miR-139-5p mimic significantly down-regulated the expression of DNMT1 and up-regulated the expression of NF2 (P<0.05). Compared with control cells, transfection of DNMT1-siRNA significantly promoted the expression of NF2 (P<0.05). Transfection of miR-139-5p mimetics or DNMT1-siRNA significantly induced U251 cell apoptosis and inhibited cell invasion (P<0.05). 【Conclusion】 miR-139-5p plays an anti-cancer role in glioblastoma, and it inhibits tumor proliferation and metastasis by targeting negative regulation of DNMT1.

Analysis on clinical features and prognosis of patients with neurofibromatosis type 2 after operation / 中国综合临床

Objective To investigate the correlation between clinical features and prognosis of patients with neurofibromatosis type 2(NF2)after operation.Methods The clinical features and prognosis of sixty patients with neurofibromatosis type 2(NF2)from 2000 to 2013 in Xi′an No.1 Hospital were analyzed.Cox proportional hazards regression model was used for variable analysis.Results The patients were followed up for 1-188 months,53 patients survived(88.3%,53/60),and 7 patients died(11.7%,7/60).Single factor analysis showed that the first symptom age,age of diagnosis,intracranial meningioma and spinal cord tumor were related to the prognosis of the patients(P<0.05).However,gender,genetic factors,skin lesions,eye diseases, postoperative hearing improvement and relief of dizziness after surgery were not correlated with the prognosis of patients(P>0.05).Spinal cord tumors or intracranial meningiomas were the independent risk factors for the prognosis of NF2 patients(P=0.042,0.037,95%CI=0.021-2.069,0.587-2.543,RR=2.475,3.663).The first symptoms age,age of diagnosis,ocular lesions were the risk factors for the occurrence of spinal cord tumors and intracranial meningiomas(P<0.05).Conclusion NF2 has many clinical symptoms,accompanied by spinal cord tumor and intracranial meningioma,which are the important prognostic factors in patients with poor prognosis.

Analysis on clinical features and prognosis of patients with neurofibromatosis type 2 after operation / 中国综合临床

Objective To investigate the correlation between clinical features and prognosis of patients with neurofibromatosis type 2(NF2)after operation.Methods The clinical features and prognosis of sixty patients with neurofibromatosis type 2(NF2)from 2000 to 2013 in Xi′an No.1 Hospital were analyzed.Cox proportional hazards regression model was used for variable analysis.Results The patients were followed up for 1-188 months,53 patients survived(88.3%,53/60),and 7 patients died(11.7%,7/60).Single factor analysis showed that the first symptom age,age of diagnosis,intracranial meningioma and spinal cord tumor were related to the prognosis of the patients(P<0.05).However,gender,genetic factors,skin lesions,eye diseases, postoperative hearing improvement and relief of dizziness after surgery were not correlated with the prognosis of patients(P>0.05).Spinal cord tumors or intracranial meningiomas were the independent risk factors for the prognosis of NF2 patients(P=0.042,0.037,95%CI=0.021-2.069,0.587-2.543,RR=2.475,3.663).The first symptoms age,age of diagnosis,ocular lesions were the risk factors for the occurrence of spinal cord tumors and intracranial meningiomas(P<0.05).Conclusion NF2 has many clinical symptoms,accompanied by spinal cord tumor and intracranial meningioma,which are the important prognostic factors in patients with poor prognosis.

A Case Study Of Auditory Brainstem Implant in a Patient with Neurofibromatosis Type Ⅱ / 听力学及言语疾病杂志

Objective To study the clinical characteristics and treatment of neurofibromatosis type Ⅱ (neuro-fibromatosis type 2 ,NF2 ,bilateral acoustic neuroma) ,and the effects of auditory brainstem implant for treating to-tal deafness after bilateral acoustic neuroma resection .Methods One case of bilateral acoustic neuroma and all clini-cal data in terms of diagnosis ,treatment and hearing -speech rehabilitation after surgery were retrospectively stud-ied .Results The patient was a thirteen years old boy .His clinical symptoms were hearing loss on the right ear ,tin-nitus ,hoarseness and gait instability three years .MRI showed space occupying lesion in the cerebellopontine angle . The postoperative pathological diagnosis was bilateral acoustic neuroma .The initial switch -on was peformed six weeks after the surgery ,and confirmed that all electrodes generated listening responses .As the extension of recov-ery time ,the correct recognition rate of patients on the natural environment sound ,vowel ,monosyllabic were on the rise and the pure tone hearing threshold gradually decreased .The vowel correct recognition rate of postoperative 6 , 9 ,12 ,24 ,and 36 months were 14% ,18% ,20% ,24% ,and 20% ,respectively .The recognition rate of monosyl-labic and open words at each postoperative rehabilitation stage were 0 .Conclusion The clinical characteristics and treatment of bilateral acoustic neuroma were different from the unilateral acoustic neuroma .The individualized treat-ment should be followed .Auditory brainstem implant could be performed in patients with post - bilateral acoustic neuroma resection .The accurate location of the cochlear complex during the surgery was the crucial point for the success of ABI .

Association of bilateral, multiple presumed retinal astrocytic proliferations with combined hamartoma of retina and retinal pigment epithelium in a 9-year-old male child with neurofibromatosis type 2.

Neurofibromatosis type 2 (NF‑2) is characterized by multifocal proliferation of neural crest‑derived cells. The characteristics finding of NF‑2 is bilateral vestibular schwannomas. Combined hamartoma of retina and retinal epithelium (CHRRPE) is another associated finding. A 9 year‑old‑male child presented with left eye decreased vision for 3 months. Visual acuity was 0.0 and 0.8 LogMAR in the right and left eye, respectively. Left fundus showed an elevated, pigmented lesion with surface wrinkling and vascular tortuosity suggestive of CHRRPE with multiple presumed retinal astrocytic proliferations in mid‑periphery. He had multiple café‑au‑lait spots. Optical coherence tomography confirmed clinical findings. Magnetic resonance imaging brain showed bilateral acoustic neuroma. Recognition of this rare finding as presenting feature of NF‑2 can lead to earlier diagnosis which is vital to appropriate surveillance and possible surgical intervention. It is recommended that children with CHRRPE be screened for NF‑2.

Neurofibromatosis: part 2 – clinical management / Neurofibromatoses: parte 2 – manejo clínico

Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1.

A primeira parte desta diretriz abordou o diagnóstico diferencial das neurofibromatoses (NF): neurofibromatose do tipo 1 (NF1), neurofibromatose do tipo 2 (NF2) e schwannomatose (SCH). As NF compartilham algumas características, como a origem neural dos tumores e sinais cutâneos, e afetam cerca de 80 mil brasileiros. O aumento do conhecimento científico sobre as NF tem permitido melhor manejo clínico e redução da morbidade das complicações, resultando em melhor qualidade de vida para os pacientes com NF. A maioria dos médicos é capaz de realizar o diagnóstico das NF, mas a variedade de manifestações clínicas e a dificuldade de se prever o surgimento e a gravidade de complicações, torna o manejo da NF um desafio para o clínico e envolve diferentes especialistas para o tratamento adequado e aconselhamento genético, especialmente a NF2 e a SCH. O presente texto sugere algumas orientações para o acompanhamento dos portadores de NF, com ênfase na NF1.

Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital Neurilemmomatosis: A Case Report

Schwannomas are the most common benign nerve sheath tumors originating in Schwann cells. With special conditions like neurofibromatosis type 2 or entity called schwannomatosis, patients develop multiple schwannomas. But in clinical setting, distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We describe 58-year-old male who presented with severe neuropathic pain, from schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent surgical treatment. We demonstrate his radiologic and clinical findings, and discuss about important clinical features of this condition. To confirm schwannomatosis, we performed brain magnetic resonance imaging, and took his familial history. Staged surgery was done for pathological confirmation and relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but different disease. There are diagnostic hallmarks of these conditions, including familial history, pathology, and brain imaging. Because of different prognosis, the two diseases must be distinguished, so diagnostic tests that are mentioned above should be performed in caution.

Neurofibromatoses: part 1 diagnosis and differential diagnosis / Das neurofibromatoses: parte 1 diagnostico e diagnostico diferencial

Neurofibromatoses (NF) are a group of genetic multiple tumor growing predisposition diseases: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH), which have in common the neural origin of tumors and cutaneous signs. They affect nearly 80 thousand of Brazilians. In recent years, the increased scientific knowledge on NF has allowed better clinical management and reduced complication morbidity, resulting in higher quality of life for NF patients. In most cases, neurology, psychiatry, dermatology, clinical geneticists, oncology and internal medicine specialists are able to make the differential diagnosis between NF and other diseases and to identify major NF complications. Nevertheless, due to its great variability in phenotype expression, progressive course, multiple organs involvement and unpredictable natural evolution, NF often requires the support of neurofibromatoses specialists for proper treatment and genetic counseling. This Part 1 offers step-by-step guidelines for NF differential diagnosis. Part 2 will present the NF clinical management.

Neurofibromatoses (NF) constituem um grupo de doenças genéticas com predisposição ao crescimento de múltiplos tumores: tipo 1 (NF1), tipo 2 (NF2) e schwannomatose (SCH). Estas doenças têm em comum a origem neural dos tumores e os sinais cutâneos. Afetam cerca de 80 mil brasileiros. O maior conhecimento científico sobre as NF tem permitido melhor manejo clínico, redução da morbidade das complicações e melhor qualidade de vida. Na maioria dos casos, os especialistas em neurologia, dermatologia, genética clínica, oncologia e medicina interna estão capacitados a realizar o diagnóstico diferencial e identificar suas principais complicações. Devido à sua variabilidade fenotípica, curso progressivo, multiplicidade de órgãos acometidos e evolução imprevisível, as NF frequentemente necessitam de especialistas em NF para o acompanhamento. A Parte 1 deste texto oferece orientações para o diagnóstico de cada tipo de NF e discute os diagnósticos diferenciais com outras doenças. A Parte 2 oferecerá orientações em relação ao manejo clínico das NF.

Bilateral Acoustic Neuroma with underlying Neurofibromatosis Type 2: A Therapeutic Challenge.

The presence of bilateral acoustic neuroma may require modification of the usual therapeutic protocol. Preservation of hearing and total removal of the tumour is much more difficult than in sporadic unilateral lesion. This case illustrates the management of a girl with bilateral acoustic neuroma with underlying neurofibromatosis type 2.

Merlina y nuevos tratamientos de schwannomas vestibulares en pacientes con neurofibromatosis tipo 2 / Merlin and new treatments for vestibular schwannomas in patients with Neurofibromatosis type 2

Los schwannomas vestibulares son tumores benignos que habitualmente se presentan en forma esporádica y unilateral, pero pueden aparecer de manera bilateral en el contexto de una neurofibromatosis tipo 2 (NF2). En aquellos asociados a NF2 se han identificado mutaciones del gen NF2 que codifica para merlina, una proteína citoplasmática que se localiza primariamente en protrusiones celulares ricas en actina, y en sitios de contacto entre células y matriz extracelular. La evidencia sugiere que merlina ejerce un rol como proteína supresora de tumores ya que regula la cascada de activación de diversos tipos de receptores de factores de crecimiento celular De esta manera, el déficit de merlina provoca un patrón de proliferación celular aumentado, alteraciones del citoesqueleto, apoptosis disminuida, y un incremento de la adhesión a la matriz extracelular. Se han desarrollado terapias clínicas para la NF2 con anticuerpos monoclonales e inhibidores dirigidos contra distintas moléculas involucradas en las cascadas de señalización celular moduladas por merlina. En este artículo se revisan y discuten los mecanismos celulares dependientes de merlina y los diversos estudios clínicos y experimentales que se han probado en pacientes con NF2.

Vestibular schwannomas are benign tumors that may occur bilaterally in the context of neurofibromatosis type 2 (NF2). A mutation in the NF2 gene coding for merlin protein has been identified in those cases associated with NF2. Merlin is a cytoplasmic protein localized in actin rich cell protrusions, and near contact sites between cells and extracellular matrix. The evidence suggests that merlin plays a role as tumor suppressor protein, regulating the activation cascade of different types of receptors for cell growth factors. Thus, merlin deficiency causes a pattern of increased cell proliferation, cytoskeletal alterations, decreased apoptosis and increased cell adhesion to the extracellular matrix. Several clinical therapies have been developed for NF2 patients including monoclonal antibodies and inhibitors directed against different molecules involved in cell signaling cascades modulated by merlin. In this article we review and discuss cellular mechanisms dependent of merlin and some clinical and experimental studies that have been studied in patients with NF2.

Molecular Characterization of the NF2 Gene in Korean Patients with Neurofibromatosis Type 2: A Report of Four Novel Mutations / 대한진단검사의학회지

BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by the NF2 tumor suppressor gene. However, the NF2 mutation characteristics in Korean patients are not sufficiently understood. In this study, we conducted a comprehensive mutational analysis in 7 Korean NF2 patients by performing direct sequencing and gene-dosage assessment. METHODS: We analyzed all exons and flanking regions of NF2 by direct sequencing and screened the deletions or duplications involving NF2 by multiplex ligation-dependent probe amplification. RESULTS: Four novel NF2 mutations, including 2 splice-site mutations (c.364-1G>A and c.886-3C>G), 1 frameshift mutation (c.524delA), and 1 missense mutation (c.397T>C; p.Cys133Arg), were identified in our patients. No large deletion or duplication was identified in our series. Subsequently, we identified an abnormal splicing product by using reverse transcription-PCR and direct sequencing in 2 patients with a novel splice-site mutation. The missense mutation c.397T>C was predicted to have harmful effects on protein function. CONCLUSIONS: The detection rate of NF2 mutations in Korean patients (57%) is similar to those in other populations. Our results provided a greater insight into the mutational spectrum of the NF2 gene in Korean subjects.

Cutaneous Plexiform Schwannomas in a Patient with Neurofibromatosis Type 2

Plexiform schwannoma is a rare benign neoplasm of the neural sheath characterized by a multinodular plexiform growth pattern. The tumor usually occurs as an isolated finding, although rare cases have been reported in association with neurofibromatosis type 2 (NF2). A 25-year-old man was admitted for foot drop. He had an asymptomatic skin-colored nodule on his neck that had been present for 10 years. His medical history included local excision of a plexiform schwannoma on his left leg in our dermatology clinic 6 years prior. A histopathological examination of the skin-colored nodule also showed the typical microscopic features of a plexiform schwannoma, including the characteristic Antoni type A areas showing frequent nuclear palisading and Verocay bodies. Magnetic resonance imaging revealed a meningioma and a vestibular schwannoma in the cranium and multiple neurofibromas on the spinal cord. Herein we report a rare case of cutaneous plexiform schwannomas in a patient with NF2.

Neurinoma del acústico diagnosticado durante el embarazo: reporte de un caso / Acoustic neurinoma during pregnancy: a case report

Los tumores cerebrales son infrecuentes durante el embarazo. Los neurinomas del acústico pueden ser sintomáticos por primera vez durante la gestación y representan el 6-8 por ciento de las neoplasias intracraneales. El objetivo de esta comunicación es presentar el caso de una primigesta adolescente que presentó sintomatología neurológica de afectación del VIII par y de fosa posterior, característica de la neurofibromatosis tipo 2.

Brain tumors are infrequent during pregnancy. Neurinomas of auditive nerve can get to be symptomatic during gestation, representing 6-8 percent of the intracranial neoplasias. The objective is to report a case of a pregnant adolescent who present a neurological symptoms of VIII pair affectation and posterior cranial fossa, characteristic of the neurofibromatosis type 2.

Implante auditivo de tronco cerebral: técnica cirúrgica e resultados auditivos precoces em pacientes com neurofibromatose tipo 2 / Auditory Brainstem Implant: surgical technique and early audiological results in patients with neurofibromatosis type 2

O implante auditivo de tronco cerebral foi desenvolvido para restaurar alguma audição útil em pacientes que apresentam ausência de nervo coclear bilateralmente. OBJETIVOS: Discutir a indicação, cirurgia e resultados em quatro pacientes submetidos à cirurgia para colocação de implante auditivo de tronco cerebral. CASUÍSTICA E MÉTODOS: Quatro pacientes com diagnóstico de schwannomas vestibulares bilaterais foram submetidos à cirurgia para colocação de Implante Auditivo de Tronco Cerebral durante o mesmo ato cirúrgico utilizado para a exérese de um dos tumores. Aspectos clínicos e técnicos e as referências anatômicas da cirurgia e os resultados auditivos foram analisados. RESULTADOS: Em todos os casos foram identificados as referências anatômicas ao forame de Luschka. As complicações cirúrgicas se resumiram à fístula liquórica em dois pacientes. Os eletrodos foram bem posicionados e a sensação auditiva foi suficiente para reconhecimento de sons e auxílio à leitura labial. CONCLUSÃO: Os resultados auditivos de nossos pacientes abrem uma perspectiva importante aos pacientes com surdez profunda bilateral sem integridade anatômica das vias auditivas centrais.

Auditory Brainstem Implants were developed to partially restore the hearing capabilities of patients without cochlear nerves bilaterally. AIM: this paper aims to discuss the clinical and surgical findings of four ABI patients. MATERIALS AND METHOD: four patients diagnosed with bilateral schwannomas received auditory brainstem implants (ABI) and had one of their tumors resected in the same surgical procedure. Clinical aspects, surgical technique, anatomic landmarks, and outcomes were analyzed. RESULTS: the anatomic landmarks were identified in all four patients in relation to the foramina of Luschka. Two patients had CSF leaks. The electrodes were well positioned and hearing sensation was good enough to allow for sound recognition and assist patients perform lip reading. CONCLUSION: the outcomes observed in our patients were quite encouraging and offer great perspectives for those suffering from deep bilateral deafness and impaired central auditory pathways.

Multicentric Spinal Schwannomas without any Evidence of Neurofibromatosis Type2

Most extracranial schwannomas are solitary, and schwannomas that occur within the context of neurofibromatosis tend to be multiple. But multiple schwannomas without any evidence of neurofibromatosis Type2 manifestation are very rare. A 49-year-old woman suffered from motor weakness and long standing low back pain and sciatica. Cervical spine MRI showed a dumbbell- shaped mass, extending from craniovertebral junction to C1, C2 spinal canal. Lumbar spine MRI showed intradural masses at L3 and L4~L5 levels. There were no clinical and radiological manifestation of Type2 neurofibromatosis. We removed these multiple tumor masses simultaneously by operation. Histologically confirmed diagnosis were all schwannomas.

Merlin Represses Ras-Induced Cyclin D1 Transcription through the Cyclic AMP-Responsive Element

Mutations in the NF2 tumor suppressor gene cause neurofibromatosis type 2, an autosomal dominant inherited syndrome predisposed to the multiple tumors of the nervous system. Merlin, the NF2 gene product was reported to block Ras-mediated cell transformation and represses Ras-induced expression of cyclin D1. However, the potential mechanism underlying the anti-Ras function of merlin on the cyclin D1 is still unclear. In this study, we investigated whether merlin decreases Ha-ras-induced accumulation of cyclin D1 at the transcriptional level, and demonstrated that merlin suppressed Ras-induced cyclin D1 promoter activity mediated by the cyclic AMP-responsive element (CRE) in SK-N-BE (2) C neuroblastoma cells. Furthermore, we found that merlin attenuated active Ras and forskolin-induced CRE-driven promoter activity. These results suggest that the transcriptional repression of the cyclin D1 expression by merlin may contribute to the inhibition of Ras-induced cell proliferation

Two Cases of Plexiform Schwannoma / 대한피부과학회지

We present two cases of plexiform schwannoma, a benign peripheral nerve sheath tumor, characterized by a plexiform growth pattern. Plexiform schwannoma must be distinguished from plexiform neurofibroma because of the propensity of the latter for malignant degeneration. Although plexiform schwannoma usually arises sporadically, it can be rarely associated with neurofibromatosis type 2. We report two cases of plexiform schwannoma. One was single sporadic lesion on the abdomen of a 28-year-old woman. The other showed multiple plexiform schwannomas associated with bilateral acoustic neuromas.

Neurofibromatosis Type 2: Long-Term Treatment Outcome

OBJECTIVE: The objective is to clarify the long-term functional outcome of NF-2 and to elucidate optimal treatment strategy. METHODS: The authors retrospectively analyzed clinical records and radiological imaging of 32 patients of NF-2 treated at from 1979 to 2000. Age at diagnosis was 30(14-54). Male to female ratio was 14:18. Mean follow-up(F/U) periods were 61(6-240) months. Four patients were lost during F/U periods. Fifty-one tumors of 29 patients were surgically treated including radiosurgery, and three patients rejected any treatment. Eleven tumors of 10 patients with non-schwannomas were managed by craniotomy, and one of them was managed by biopsy only. Among 21 tumors of 19 patients with schwannomas, 16 tumors of 14 patients were vestibular schwannomas(VS), one trigeminal schwannoma, and four spinal schwannomas. Fourteen tumors with 13 patients were managed by radiosurgery. RESULTS: Presenting symptoms were hearing problem(44%, 14/32 patients), motor or sensory change (25%, 8/32 patients), and visual symptoms (15%, 5/32 patients). Long-term functional outcome was poor (KPS; median 46.6). Six patients died during follow periods and the cause of death was aspiration pneumonia related to lower cranial palsy or high cervical cord lesion(except 1 case; suicide). In 17 patients, 7 patients of initial hearing had preserved after any treatment modalities, another 10 patients had deteriorated hearing function. In facial nerve function, 12 patients except one patient deteriorated after surgical resection. Even though facial-hypoglossal anastomosis was performed in two patients, there was no improvement of facial nerve function. CONCLUSION: Long-term results of NF-2 patients were unfavorable. The early detection of the tumor, regular F/U of patients and individually refined management are important for the optimal treatment of NF-2 patients.

Multiple Plexiform Schwannomas Associated with Neurofibromatosis Type 2: A case report

Plexiform schwannoma is a rare benign tumor arising from the peripheral nerve sheath and characterized by a multinodular and plexiform growth pattern. This tumor usually arises sporadically. In rare cases, plexiform schwannomas have been associated with neurofibromatosis type 2. Plexiform schwannoma should be differentiated from plexiform neurofibroma, because the latter is pathognomonic tumor of neurofibromatosis type 1 and has a potential of malignant transformation. We report a case of multiple plexiform schwannomas associated with bilateral acoustic neuromas and meningioma.

Germline Mutations of the NF2 Gene in Korean Neurofibromatosis 2 Patient / 대한암학회지

PURPOSE: Neurofibromatosis 2(NF2) is an autosomal dominant disease characterized by development of bilateral acoustic neuroma and various central nervous system tumors such as meningiomas, ependymomas, and schwannomas. Recent cloning of the gene responsible for NF2, the NF2 gene, permits the presymptomatic genetic diagnosis of affected individuals by direct analysis of the gene. This paper was intended to identify germline mutations in Korean NF2 patients. MATERIALS AND METHODS: We collected blood samples from 15 clinically diagnosed NF2 patients treated at the Department of Neurosurgery, Seoul National University Hospital. Purified genomic DNA samples were analyzed for mutations of the NF2 gene by using polymerase chain reaction(PCR)-single strand conformation polymorphism(SSCP) method followed by direct DNA sequencing. RESULTS: We were able to identify germline mutation of the NF2 gene in one patient. The mutation identified was 1 base pair deletion(A) at codon 318, resulting in premature stop codon due to frameshift. CONCLUSION: Identification of the germline mutation in NF2 gene should enable us to test all individual family members at risk to determine whether or not they carry the mutant NF2 gene.